1. Field of the Invention
This invention relates to a fluorescence detecting system in which excitation light is projected onto a part to be observed of an organism, and then the intensity of auto fluorescence emitted from intrinsic pigment in the part is measured. Tumor is diagnosed on the basis of the intensity of the auto fluorescence measured.
2. Description of the Related Art
There have been made various investigations on photodynamic diagnosis. The photodynamic diagnosis is a technique in which a photosensitive material (ATX-S10, 5-ALA, NPe6, HAT-D01, Photofrin-2 or the like) which has affinity to tumor and emits fluorescence when excited by light is first administered to the tumor as a fluorescence diagnosis agent, excitation light having a wavelength in the exciting wavelength range of the photosensitive material is projected onto the tumor to cause the fluorescence diagnosis agent collected in the tumor, and the tumor is diagnosed on the basis of an image which is formed by the fluorescence and shows the location and the area of infiltration of the diseased part.
A fluorescence diagnosis system for carrying out such photodynamic diagnosis is disclosed, for instance, in Japanese Patent Publication No. 63(1988)-9464 and Japanese Unexamined Patent Publication Nos. 1(1989)-136630 and 7(1995)-59783. The fluorescence diagnosis system basically comprises a excitation light projecting means which projects excitation light having a wavelength in the exciting wavelength range of the photosensitive material onto an organism, an image taking means which takes a fluorescence image of the organism formed by fluorescence emitted from the photosensitive material and an image display means which displays a fluorescence image on the basis of output of the image taking means. Such a fluorescence diagnosis system is generally incorporated in an endoscope or an operative microscope.
Further there has been proposed a technique of diagnosing tumor in which excitation light having a wavelength in the exciting wavelength range of pigment inherent to an organism is projected onto the organism without administering any photosensitive material to the organism and an image of the location and the area of infiltration of the diseased part is displayed on the basis of auto fluorescence emitted from the pigment, and tumor is diagnosed on the basis of the fluorescence image.
Further there has been known a fluorescence diagnosis system in which, without taking a two-dimensional fluorescence image, the intensity of fluorescence is detected for each point on an organism and whether the point is tumor-bearing is determined according to the intensity of fluorescence. See, for instance, Japanese Unexamined Patent Publication No. 9(1997)-149891.
In such a fluorescence diagnosis system, since the surface of a part of an organism is generally uneven. the distance between the excitation light projecting means and the part to be observed differs from point to point and accordingly illuminance of the excitation light generally differs from point to point. The intensity of fluorescence is generally proportional to the illuminance of the excitation light and the illuminance of the excitation light reduces in reverse proportion to the square of the distance from the light source. Accordingly, there cases where a normal part near to the light source emits fluorescence stronger than that emitted from a diseased part remote from the light source or fluorescence from a diseased part positioned inclined to the excitation light is extremely weakened. Thus nonuniformity of illuminance of the excitation light can lead to misdiagnosis.
In order to compensate for change in intensity of fluorescence due to difference in distance from the light source, there have been proposed fluorescence diagnosis systems such as disclosed in Japanese Unexamined Patent Publication No. 62(1987)-247232, Japanese Patent Publication No. 3(1991)-58729 and the like. In the fluorescence diagnosis system disclosed in the former patent publication, excitation light is projected onto a part of an organism which has been given a photosensitive material having a strong affinity to a diseased part, emitted fluorescence and reflected excitation light are detected and image processing operation is carried out on the basis of a division between the fluorescence component and the reflected light component. By such a division, terms related to the distance from the light source can be cancelled. However since there remains a term related to the reflectance of the part exposed to the excitation light in the result of the division, there still remains a problem that a fluorescence image accurately reflecting the distribution of the fluorescence diagnosis agent cannot be obtained.
In the system disclosed in "FLUORESCENCE IMAGING OF EARLY LUNG CANCER" (Annual International Conference of the IEEE Engineering and Biology Society, Vol. 12, No. 3, 1990), auto fluorescence emitted from intrinsic pigment of a part to be observed in an organism is divided into a component having a wavelength in a green region (will be referred to as "the green region component G", hereinbelow) and a component having a wavelength in a red region (will be referred to as "the red region component R", hereinbelow), and carries out an image processing operation on the basis of division between the red region component R and the green region component G, and a result of the division is displayed. That is, since in a spectrum of auto fluorescence emitted from a diseased part, the intensity of the green region is extremely weaker than that in a spectrum of auto fluorescence emitted from a normal part, the reduction rate of the green region component G is much larger than of the red region component R in the auto fluorescence emitted from the diseased part. Accordingly by division of R/G, the fluorescence from the diseased part can be specifically extracted and an image can be formed on the basis of the extracted fluorescence. In the system, though the term of fluorescence intensity depending on the distances between the excitation light source and the part to be observed of the organism and between the fluorescence receiving section and the part to be observed of the organism can be cancelled, there is a problem that the S/N ratio becomes extremely low due to an extremely weak auto fluorescence at the diseased part.
In "Fluorescence Image Diagnosis of Cancer Using Red/Green Ratio" reported in 16-th Conference of Japanese Laser Medical Society, 1995 (Tokyo Medical College, Hamamatsu Photonix), it is proposed to strengthen red fluorescence at a diseased part by use of a fluorescence diagnosis agent which is accumulated in a diseased part and emits red fluorescence and to carry out operation of R/G. In this system, there can be obtained a fluorescence image in which the intensity of fluorescence from the diseased part is increased as compared with the system described in the aforesaid "FLUORESCENCE IMAGING OF EARLY LUNG CANCER".
By use of operation of R/G, the term of fluorescence intensity depending on the distances between the excitation light source and the part to be observed of the organism and between the fluorescence receiving section and the part to be observed of the organism can be cancelled.
However, since the green auto fluorescence at the diseased part is extremely weak, there still remains a problem that operation of R/G sometimes results in R/0, which is apt to lead to operation errors.